Skinned coronary smooth muscle: calmodulin, calcium antagonists, and cAMP influence contractility

The effects of Ca2+, calmodulin, cAMP, the catalytic subunit of cAMP-dependent protein kinase (CSU) and some Ca2+ antagonists were studied in chemically (Triton X-100) skinned coronary smooth muscle. Calmodulin increased the Ca2+ responsiveness of the muscle fiber as indicated by the reduction in the threshold as well as the half-maximal activating Ca2+ concentration. Trifluoroperazine, a calmodulin antagonist, inhibited Ca2+-calmodulin-induced contraction. Both cAMP and CSU were effective inhibitors of contraction induced at an intermediate Ca2+ concentration. Fendiline, a Ca2+-antagonist, at 2 x 10(-4) M produced a significant inhibitory effect, which was reduced by increasing the Ca2+ concentration. From other Ca2+ antagonists tested, W-7, but not D600 and verapamil, produced some inhibitory effect. The data indicate that the response of skinned coronary smooth muscle to Ca2+, calmodulin and cAMP are similar to those obtained with other skinned smooth muscles. Furthermore, skinned fiber preparation can serve as a useful tool to investigate possible direct effects of drugs on the activating and regulatory systems in smooth muscle.